Anti-thymocyte globulin for conditioning in matched unrelated donor hematopoietic cell transplantation provides comparable outcomes to matched related donor recipients.

Rabbit anti-thymocyte globulin (ATG) is used as prophylaxis against GVHD following allogeneic hematopoietic cell transplantation (HCT). At our institution, ATG is exclusively used in the conditioning of matched unrelated donor (URD) transplant recipients. A total of 50 URD HCT recipients who received ATG (ATG group) were retrospectively compared with 48 matched related donor (MRD) HCT recipients who did not receive ATG (no ATG group). There were no significant differences between the groups in rates of day 100 mortality, acute GVHD or relapse. Chronic GVHD incidence was significantly lower in the ATG group (P = 0.007). At a median follow-up of 36 months in the entire cohort, 50% patients are alive in the ATG group and 63% of the patients are alive in the no ATG group (P = 0.13). We conclude that the administration of ATG to patients undergoing URD HCT preserves the anti-leukemia benefit of the transplant, while reducing the risk of developing GVHD, resulting in OS rates that are comparable to MRD HCT recipients.

Expectant management of intramural ectopic pregnancy.

BACKGROUND: Intramural ectopic pregnancy is unusual, difficult to diagnose, and associated with a high rate of uterine rupture. CASE: A 35-year-old, gravida 3, para 0-0-2-0 was diagnosed with intramural ectopic pregnancy by ultrasound showing a gestational sac surrounded completely by myometrium. It was confirmed by laparoscopy. With expectant management, the gestation resolved spontaneously. CONCLUSION: Early diagnosis by ultrasound of intramural ectopic pregnancy permits expectant management which, if successful, would aid in maintaining fertility.

Microbiology of otitis externa.

Microbiologic and clinical data from 26 patients with otitis externa were prospectively evaluated. Specimens were processed for aerobic and anaerobic bacteria. Bacterial growth was noted in 23 specimens. A total of 33 aerobic and 2 anaerobic bacteria were recovered. Aerobic bacteria only were isolated in 21 (91%) patients, anaerobic bacteria only in 1 (4%), and mixed aerobic and anaerobic bacteria in 1 (4%). The most common isolates were Pseudomonas aeruginosa (14 instances), Staphylococcus aureus (7), Acinetobacter calcoaceticus (2), Proteus mirabilis (2), Enterococcus faecalis (2), Bacteroides fragilis (1), and Peptostreptococcus magnus (1). One isolate was recovered in 13 (57%) patients, 2 isolates in 8 (35%), and 3 isolates in 2 (9%). These data illustrate the polymicrobial nature of otitis externa in about half of the patients and the role of anaerobic bacteria in 8% of them. Further studies are warranted to evaluate the therapeutic implications of these findings.

Avulsion of the ischial apophysis.

Avulsion of the ischial apophysis is a rare injury. We report the successful treatment of an avulsion of the ischial apophysis by open reduction and internal fixation.

Fimbrial-mediated colonization of murine teeth by Actinomyces naeslundii.

Groups of mice fed diets high in sucrose or glucose were orally inoculated with 10(10), 10(9) or 10(8) colony-forming units of one of the following Actinomyces naeslundii strains possessing the type 1 (T1+) and/or the type 2 (T2+) fimbriae: T14VJ1 (T1+, T2+), 5519 (T1+), 5951 (T2+), and 147 (non-fimbriated). Ninety-six hours after inoculation their upper jaws were cultured to look at the implantation of each of these strains on the teeth. In mice fed a sucrose diet, regardless of the presence or absence of fimbriae, each bacterial strain colonized 100% of the mice at the highest inoculation doses of the infecting organism. But at a dose of 10(8), T14V-J1 was the only strain which colonized 100% (12/12) of the mice, 5519 colonized 10/11, 5951 colonized 9/11 and 147 colonized 7/11. These differences were not statistically significant. When mice were fed a high-glucose diet, 100% infection was achieved with strains T14V-J1, 5519 and 5951 only at the highest dose of 10(10) colony-forming units. Strain 147 colonized in 8/9 of the mice at that dosage. At lower dosages, no bacterial strain implanted in 100% of the mice. In the glucose experiment at a dose of 10(8), strains expressing the T1 fimbriae implanted significantly better than strains without the T1 fimbriae. At a dose of 10(9) colony-forming units, the parent strain T14V-J1 implanted significantly better than strains without the T1 fimbriae. Similarly, strain 5519 (T1+) implanted significantly better than 5951 and implanted better than 147, although the difference was not significant. These results suggest that while the presence of the T1 and T2 fimbriae may confer some advantage in the establishment of these organisms in vivo, even the strains without fimbriae were able to colonize. Strains T14VJ1 and 5519 were found to bind well to hydroxyapatite treated with mouse saliva, while strains 5951 and 147 did not. Only T2 fimbriated strains T14V-J1 and 5951 exhibited a lactose-reversible coaggreation with indigenous strains of enterococci that may contribute to the elevated levels of colonization of strain 5951 in vivo.

A multi-center clinical trial of a new chairside test in distinguishing between diseased and healthy periodontal sites. II. Association between site type and test outcome before and after therapy.

The aim of the present study was to evaluate the association between the outcome of a chairside test measuring gingival crevicular fluid (GCF) levels of the enzyme aspartate aminotransferase (AST) and other clinical measures of disease including probing depth, severity of inflammation, and GCF flow before and after therapy. We studied 91 patients with moderate to severe periodontitis. Eight sites with probing depths between 5 mm and 8 mm and obvious signs of inflammation were selected and designated diseased sites. Four sites with probing depth < or = 3 mm with no or minimal signs of inflammation were selected and designated non-diseased sites in patients. Thirty healthy individuals were enrolled and four sites in each were selected and designated healthy controls. Patients were treated with scaling and root planing and control subjects with supragingival prophylaxis. Measurements including GCF volume, gingival inflammation, and probing depth were performed at screening baseline, 1 week later at pretreatment baseline, and at weeks 2 and 4 after treatment. AST content of GCF was measured using a chairside colorometric test. It was concluded that the outcome of the test is an effective objective measure distinguishing between diseased sites and non-diseased sites in patients and control subjects when evaluated both prior to and following application of therapy. Use of this simple chairside test, when combined with other standard diagnostic procedures, provides an objective measurement permitting improved capacity to distinguish between diseased and non-diseased periodontal sites, and to better assess and monitor the outcome of therapy.

Prevotella intermedia fimbriae mediate hemagglutination.

Our earlier studies demonstrated that clinical strains of Prevotella intermedia, isolated from human periodontal pockets, possess various types of fimbria (surface appendages) as determined ultrastructurally. These bacteria have the ability to agglutinate selected mammalian erythrocytes. Hemagglutinating activity exhibited by these cells may be attributable to these surface structures. Strain 17, which possess fimbriae of 8 nm in diameter and readily agglutinates human, monkey, sheep, rabbit, and mouse erythrocytes was selected to determine whether these fimbriae possessed the hemagglutinating activity. Fimbriae were mechanically sheared, concentrated by ammonium sulfate precipitation, solubilized in 10 mM Tris-HCl buffer containing 0.5% deoxycholate and partly purified by ultracentrifugation in a 10-50% linear sucrose gradient. Isolated fimbriae banded at a density of 1.20-1.15 g/ml, appeared fairly uniform ultrastructurally, and possessed hemagglutinating activity. The hemagglutinating activity of P. intermedia whole cells and isolated fimbriae was reduced by treatment with proteases and eliminated by treatment with heat at 80 degrees C for 10 min. The optimal pH for the hemagglutination was 7.0. In the process of hemagglutination, P. intermedia whole cells and isolated fimbriae bound to rabbit erythrocytes as observed by: (a) decrease in the hemagglutinating activity of bacterial whole cells and isolated fimbriae after incubation with rabbit erythrocytes, (b) increase in hemagglutinating activity of the red cells used for absorption, and (c) the presence of P. intermedia whole cells and fimbriae on red cells after absorption as revealed by immunoelectron microscopy. Both the immune immunoglobulin G of the rabbit polyclonal anti-fimbriae antibody and the immune immunoglobulin G and its Fab fragments of the murine monoclonal anti-fimbriae antibody were effective inhibitors of hemagglutination mediated by isolated fimbriae. Immunogold labeling showed that the monoclonal antibody bound specifically to P. intermedia fimbriae. These results collectively suggest that the hemagglutination exhibited by P. intermedia may be attributable to the fimbriae or the fimbrial-associated components.

Coaggregation of Candida albicans with oral Actinomyces species.

Eight strains of Actinomyces were examined for their ability to coaggregate in vitro with four strains of Candida albicans. The Actinomyces coaggregated to various degrees with all of the Candida strains. Exposure of the Candida but not the Actinomyces to heat, trypsin, proteinase K, amphotericin B or trichodermin abolished coaggregation. All sugars tested did not inhibit any of the reactions. All coaggregating pairs were disaggregated by the addition of SDS, but nonionic detergents had no effect. The addition of urea or EDTA completely reversed coaggregation. Actinomyces strains were sensitive to periodate oxidation, whereas the Candida strains were unaffected. These data suggest that the coaggregations involve a protein on the Candida surface that may interact with carbohydrates or carbohydrate-containing molecules on the surface of the Actinomyces. These observations expand the known range of intergeneric coaggregations occurring between human oral microbes and indicate that coaggregation of C. albicans and Actinomyces may be an important factor in oral colonization by this yeast.

Inhibition of adherence of Actinomyces naeslundii (Actinomyces viscosus) T14V-J1 to saliva-treated hydroxyapatite by a monoclonal antibody to type 1 fimbriae.

A monoclonal antibody to Actinomyces naeslundii (A. viscosus) T14V-J1 type 1 fimbriae, capable of inhibiting the adherence of this bacterium to salivary proline-rich protein-treated hydroxyapatite, was generated by immunization of SWR mice with A. naeslundii 55-19, a strain derived from T14V-J1 that possess only type 1 fimbriae. Supernatants of hybridomas were screened for reactivity with purified type 1 fimbriae. An IgG monoclonal antibody, 86-49E, blocked the adsorption of the parent strain to proline-rich protein-treated hydroxyapatite by 77% with 1.0 microgram/ml of the monoclonal antibody; the Fab fragment derived from this monoclonal antibody inhibited adherence by 38% at the same concentration. Similarly, the adherence of strain 55-19 was inhibited by 100% and 64% to proline-rich protein-treated hydroxyapatite with 1.0 micrograms/ml of IgG and Fab fragments respectively. Control monoclonal antibody to the subunit of type 1 fimbriae, as well as to Actinobacillus actinomycetemcomitans caused only minimal adherence inhibition. Monoclonal antibody 86-49E also agglutinated both type 1 fimbriae-bearing strains of A. naeslundii T14V-J1 and 55-19 but not strains 59-51 and 147, which lack type 1 fimbriae. Further confirmation of the specificity of monoclonal antibody 86-49E was obtained using these fimbria-deficient mutant strains in an enzyme-linked immunosorbent assay, with the monoclonal antibody binding only to strains possessing type 1 fimbriae. Immunogold labeling in conjunction with electron microscopy suggested binding of monoclonal antibody 86-49E occurring near the distal end of the fimbriae. In contrast, when a monoclonal antibody specific for the type 1 fimbrial subunit but not capable of adherence inhibition was used together with 86-49E in double-labeling experiments, extensive labeling of the fimbriae by the subunit antibody was noted. These data suggest that a monoclonal antibody specific for the type 1 fimbriae of A. naeslundii that is capable of binding to a discrete site on the fimbriae has the capacity to inhibit the adsorption of this organism to saliva-treated hydroxyapatite.

A multicenter clinical trial of PerioGard in distinguishing between diseased and healthy periodontal sites. (I). Study design, methodology and therapeutic outcome.

We designed and performed a multicenter clinical trial to determine the relationship between measurements of the level of the enzyme aspartate aminotransferase (AST) in gingival crevicular fluid (GCF) to other measures used to detect periodontal disease and monitor outcome of treatment, including pocket depth and gingival inflammation. 32 periodontitis patients were enrolled at the University of Washington, Seattle, 30 at the University of Florida, Gainesville, and 34 at the University of Illinois, Chicago. 10 periodontally normal control subjects were enrolled at each location. 8 diseased and 4 healthy sites were designated for study in each patient and 8 healthy sites designated in each control subject. Measures of disease included pocket depth, severity of gingival inflammation, and GCF volume. AST levels were measured using the PerioGard test kit. Clinical measurements were made and GCF samples harvested and tested 2x before and 2x after therapy consisting of scaling and root planing under local anesthetic. Specific design and other issues are discussed, including selection of patients and control subjects, sample size, selection of experimental test sites, methods for assessment of diseased and therapeutic improvement, harvesting of GCF and selection of appropriate biostatistical methods for data analysis. Demographics of the patient populations at the 3 locations are reported. As expected, therapy induced only negligible changes in the measures of disease at healthy sites in control subjects, and relatively minor improvement in healthy sites in patients. In contrast, statistically significant improvement relative to pretreatment baseline status in all 3 measures of disease was observed for diseased sites at all 3 study locations with all p-values less than 0.0002. The magnitude of improvement was comparable to that reported previously by others. The % of PerioGard-positive sites decreased significantly between the screening baseline and both post-treatment visits for patients at all 3 locations, with p values of 0.0001 to <0.0008.

Drinking-related problems in the United States: description and trends, 1984-1990.

OBJECTIVE: This study uses two national alcohol surveys to assess rates of drinking problems from 1984 to 1990, to examine any changes in reports of drinking problems within demographic subgroups, and to evaluate the role of alcohol use versus demographic variables in predicting drinking problems in the 1990 survey only. METHOD: Data were obtained from two national alcohol surveys that utilized household probability samples within the 48 contiguous states in 1984 and 1990. Weights to adjust for design effects and nonresponse were applied to both samples of current drinkers. RESULTS: No significant changes were found for reports of three or more dependence symptoms (6.7% in 1984, 7.6% in 1990) or two or more social consequences (10.9% in 1984, 12.8% in 1990). Significant increases in reports of two or more social consequences were found for younger people, never married individuals and respondents who were not employed. A significant increase in reports for three or more dependence symptoms was also found for the unemployed group. Based on a cross-sectional analysis of the 1990 survey only, alcohol use variables were significant predictors of drinking problems. With the exception of younger age, demographic characteristics did not significantly predict alcohol problems. CONCLUSIONS: Although drinking problems are pervasive, they may not be sensitive to immediate changes in alcohol consumption. One explanation may be the changing social climate around drinking to which most drinkers have been, and are continuing to be, exposed.

Ethnic differences in performance of screening instruments for identifying harmful drinking and alcohol dependence in the emergency room.

This study examines sensitivity and specificity figures associated with screens used to predict harmful drinking and alcohol dependence among current drinkers. The study population comes from a probability sample of emergency room patients in Jackson, MS. Data are presented by gender and injury status (injured versus noninjured) for Blacks and for Whites. The Composite International Diagnostic Interview was used to assess ICD-10 criteria for harmful drinking and alcohol dependence, which were taken as standards. Predictors include screening instruments (CAGE, AUDIT, brief MAST, TWEAK, and History of Trauma Scale), breathalyzer reading, self-reported consumption before the injury or noninjury event, quantity and frequency of drinking, and an abbreviated alcohol dependence experiences measure used in general population surveys. Single items from these screening instruments were also tested as predictors. Overall, the TWEAK and the AUDIT performed best in terms of sensitivity and specificity, but variation across subgroups suggests that the search for a good screening instrument for general use must be continued.

Research, technology transfer, and dentistry.

The periodontal discipline illustrates the need for dentists to be doctors specializing in oral medicine. Research findings are tending toward more complex and possibly lengthy treatment with drugs and/or growth factors, necessitating a curriculum with more emphasis on pharmacology, medical management, critical review of clinical trial results, and evaluation of risk-benefit ratios.

Treatment of subjects with refractory periodontal disease.

The aim of the present study was to evaluate the effect of non-surgical periodontal therapy with the adjunct of a selected antibiotic in subjects diagnosed with refractory periodontal disease. 21 subjects were selected for the study; all had a history of periodontal surgery, tetracycline therapy, and regular maintenance by a periodontist. When disease activity was detected, a bacterial sample was taken and a whole plaque susceptibility test was performed. Before the outcome of the susceptibility test the subjects were assigned to either antibiotic or placebo therapy. All subjects received scaling and rootplaning prior to antibiotic or placebo therapy. Based on the susceptibility test, subjects in the antibiotic group were treated either with Augmentin or clindamycin. The results demonstrated that in subjects with refractory periodontal disease there was no significant difference (N.S.) in the proportion of sites losing attachment before and after treatment (11.3% and 12.4%, respectively) over a 2-year post therapy observation period. However, the proportion of sites showing gain of attachment increased from 0.9% before therapy to 5.1% (p = 0.029) following selective antibiotic therapy when combined with scaling and rootplaning. The remainder of sites showed no change between pre- and post-therapy monitoring periods. The progression of attachment loss in the active sites could not be completely stopped over the entire 2-year period. After 12-15 months following therapy, there was a tendency towards new loss of attachment and an increase of pocket depth. However, all 4 subjects treated with placebo drug demonstrated continuous deterioration and had to be retreated. Although the proportion of sites losing attachment decreased from 5.1% to 2.3% (N.S.), the proportion of sites gaining attachment also decreased from 2.0% to 1.0% (N.S.). The results suggest that scaling and rootplaning together with selected antibiotic therapy repeated every 12-15 months may be beneficial for these subjects although it may not completely stop progressive attachment loss.

The demographic distribution of US drinking patterns in 1990: description and trends from 1984.

OBJECTIVES: Since 1981, per capita consumption of alcohol (based on sales figures) has decreased in the United States. This study describes drinking patterns in the 1990 national alcohol survey by demographic correlates and assesses changes in drinking patterns from the 1984 survey. METHODS: Data were obtained from a national household probability sample within the 48 contiguous states; face-to-face interviews were conducted with 2058 adults. The instrument contained questions pertaining to the respondent's background, attitudes toward alcohol, and use of alcohol. RESULTS: The proportions of current drinkers; current drinkers of wine, beer, and liquor; weekly drinkers; and drinkers who reported having five or more drinks per occasion at least once a week were significantly lower in 1990 than in 1984. These changes remained significant when demographic characteristics were controlled by logistic regression. The findings held for Whites only; there were no significant trends for Blacks or Hispanics. CONCLUSIONS: While there has been a downward turn in alcohol use in the United States, the correlates of alcohol use have not changed. How these shifts affect alcohol-related problems is an important area for future research.

Modeling the relationship between clinical, microbiologic, and immunologic parameters and alveolar bone levels in an elderly population.

A cross-sectional periodontal study of 74 subjects aged 65 to 75 years was performed. Clinical data were collected and related to microbiological and immunological data. A statistical model (step-wise multiple regression) of factors related to bone loss was created initially using clinical data only; then by adding either the microbiologic or immunologic data; and then by using clinical, microbiologic, and immunologic data together. When only clinical data were considered, three factors were found to have significant positive correlations with bone loss. Tooth mobility accounted for 17% of the variability in the alveolar bone level measurements, probing depth for 12%(r2), and plaque index for 3%, for a total of 32% of the variability explained by these clinical factors. Tooth mobility and probing depth were clinical factors which remained significant in the model when the microbiological data were also considered. As percentages of the total cultivable microbiota, E. corrodens (r2 = 14%) and black-pigmenting Prevotella intermedia (r2 = 4%) correlated positively with alveolar bone loss. The addition of the microbiologic data only increased the r2 to 33%. When immunological data were considered with the clinical data, pocket depth and tooth mobility were the clinical parameters which remained in the model. IgG antibody levels to P. gingivalis W83 and/or 381 (r2 = 24%) A. actinomycetemcomitans 627 (r2 = 2%) were the significant immunologic measures having a positive correlation with bone loss. Anti-F. nucleatum levels had a significant negative correlation. A total of 50% of the variability in alveolar bone level was accounted for in the model by the addition of specific serum antibody levels to subgingival plaque microorganisms. When clinical, microbiological, and immunological measurements were all considered together, antibody to P. gingivalis W83 and/or 381 (r2 = 42%), percentage of B-lymphocytes (r2 = 3%), probing depth (r2 = 4%), anti-E. corrodens levels (r2 = 2%), and anti-P. gingivalis 33277 levels (r2 = 4%) all had significant positive correlation with loss of alveolar bone. The number of enteric bacteria, anti-F. nucleatum levels, and anti-P. intermedia levels each had a significant negative correlation with alveolar bone heights. The r2 for this model was 75%. These results indicated that antibody levels to subgingival plaque microorganisms and tooth mobility were the best predictors of bone loss in the elderly patients tested in this study.

A role for antibiotics in the treatment of refractory periodontitis.

Refractory periodontitis is considered by many investigators to be a separate disease entity that is descriptive of a particular patient who has multiple sites, rather than a few individual sites, that do not respond to conventional periodontal treatment modalities. Such patients continue to demonstrate loss of attachment and alveolar bone despite frequent periodontal treatment which includes surgical intervention, scaling and root planing, and often systemically-administered tetracycline. Controlled clinical studies have demonstrated that both clindamycin-hydrochloride and amoxicillin/clavulanate potassium (Au) are beneficial when used in conjunction with periodontal scaling. Gordon et al. found improvements in attachment levels, inflammation, suppuration, and a decrease in pocket depths for up to 2 years following a 7-day course of clindamycin given in conjunction with a full-mouth scaling. The incidence of disease activity decreased from an annual rate of 8% of all sites prior to antibiotic treatment to 0.5% after treatment. Magnusson, reporting on a similar group treated with a 14-day course of Au, found an average loss of attachment of 2.2 mm and an increase in pocket depth of 1.5 mm in sites demonstrating disease progression prior to antibiotic treatment. At 3 months post-antibiotic therapy, these sites had regained an average of 2 mm of attachment and pocket depths had decreased an equivalent amount. Both attachment levels and pocket depths remained relatively stable for up to 12 months post-therapy. In an ongoing study, 30 subjects with refractory periodontitis were treated with either clindamycin or Au in conjunction with scaling or scaling plus a placebo. Prior to antibiotic treatment, but while being scaled at 3-month intervals, sites with disease activity lost an average 2.4 mm of attachment. At 3 months post-treatment, the clindamycin-treated group showed an average gain of 2.1 mm, the Au-treated group gained 1.9 mm, and the scaling group gained 1.4 mm in attachment. The clindamycin group remained relatively stable for up to 21 months and the Au group remained stable for about 15 months without additional treatment. Five of the 6 subjects treated with scaling alone required additional treatment within 9 months. Preliminary analyses have indicated that at least two patterns or rates of attachment loss may be associated with refractory periodontitis and that each pattern may be indicative of a different microflora. The pattern associated with a relatively rapid loss of attachment was characterized by a Gram-negative flora which contained spirochetes, P. intermedia, and Fusobacterium species.(ABSTRACT TRUNCATED AT 400 WORDS)